Double bipolar configuration for atrial fibrillation annotation

ABSTRACT

Catheterization of the heart is carried out by inserting a probe having electrodes into a heart of a living subject, recording a bipolar electrogram and a unipolar electrogram from one of the electrodes at a location in the heart, and defining a window of interest wherein a rate of change in a potential of the bipolar electrogram exceeds a predetermined value. An annotation is established in the unipolar electrogram, wherein the annotation denotes a maximum rate of change in a potential of the unipolar electrogram within the window of interest. A quality value is assigned to the annotation, and a 3-dimensional map is generated of a portion of the heart that includes the annotation and the quality value thereof.

CROSS-REFERENCE TO RELATED APPLICATIONS

This Application is a Continuation of U.S. patent application Ser. No.14/585,828, filed Dec. 30, 2014, which claims priority to U.S.Provisional Application No. 61/932,877, filed 29 Jan. 2014, which isherein incorporated by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

-   -   This invention relates to cardiac physiology. More particularly,        this invention relates to the evaluation of electrical        propagation in the heart.

2. Description of the Related Art

TABLE 1 Acronyms and Abbreviations CFAE Complex Fractionated AtrialElectrogram ECG Electrocardiogram EGM Electrogram FIR Finite InfiniteResponse IIR Infinite Impulse Response LAT Local Activation Time WCTWilson Central Terminal

Cardiac arrhythmias such as atrial fibrillation are an important causeof morbidity and death. Commonly assigned U.S. Pat. No. 5,546,951, andU.S. Pat. No. 6,690,963, both issued to Ben Haim and PCT application WO96/05768, all of which are incorporated herein by reference, disclosemethods for sensing an electrical property of heart tissue, for example,local activation time, as a function of the precise location within theheart. Data are acquired with one or more catheters having electricaland location sensors in their distal tips, which are advanced into theheart. Methods of creating a map of the electrical activity of the heartbased on these data are disclosed in commonly assigned U.S. Pat. No.6,226,542, and U.S. Pat. No. 6,301,496, both issued to Reisfeld, whichare incorporated herein by reference. As indicated in these patents,location and electrical activity is typically initially measured onabout 10 to about 20 points on generate a preliminary reconstruction ormap of the cardiac surface. The preliminary map is often combined withdata taken at additional points in order to generate a morecomprehensive map of the heart's electrical activity. Indeed, inclinical settings, it is not uncommon to accumulate data at 100 or moresites to generate a detailed, comprehensive map of heart chamberelectrical activity. The generated detailed map may then serve as thebasis for deciding on a therapeutic course of action, for example,tissue ablation, to alter the propagation of the heart's electricalactivity and to restore normal heart rhythm.

Catheters containing position sensors may be used to determine thetrajectory of points on the cardiac surface. These trajectories may beused to infer motion characteristics such as the contractility of thetissue. As disclosed in U.S. Pat. No. 5,738,096, issued to Ben Haim,which is incorporated herein in its entirety by reference, mapsdepicting such motion characteristics may be constructed when thetrajectory information is sampled at a sufficient number of points inthe heart.

Electrical activity at a point in the heart is typically measured byadvancing a multiple-electrode catheter to measure electrical activityat multiple points in the heart chamber simultaneously. A record derivedfrom time varying electrical potentials as measured by one or moreelectrodes is known as an electrogram. Electrograms may be measured byunipolar or bipolar leads, and are used, e.g., to determine onset ofelectrical propagation at a point, known as local activation time.

However, determination of local activation time as an indicator ofelectrical propagation becomes problematic in the presence of conductionabnormalities. For example, atrial electrograms during sustained atrialfibrillation have three distinct patterns: single potential, doublepotential and a complex fractionated atrial electrograms (CFAE's). Thus,compared to a normal sinus rhythm signal, an atrial fibrillation signalis extremely complex, as well as being more variable. While there isnoise on both types of signal, which makes analysis of them difficult,because of the complexity and variability of the atrial fibrillationsignal the analysis is correspondingly more difficult. On the otherhand, in order to overcome the atrial fibrillation in a medicalprocedure, it is useful to establish possible paths of activation wavestravelling through the heart representing atrial fibrillation. Oncethese paths have been identified, they may be blocked, for example, byappropriate ablation of a region of the heart. The paths may bedetermined by analysis of intra-cardiac atrial fibrillation signals, andembodiments of the present invention facilitate the analysis.

SUMMARY OF THE INVENTION

While the description herein is, for simplicity, directed to situationswhere atrial fibrillation is occurring, those having ordinary skill inthe art will be able to adapt the description, mutatis mutandis, forother types of fibrillation.

Embodiments of the present invention simultaneously acquireelectropotential signals in the heart using a catheter having amultiplicity of electrodes at its distal end, each electrode generatinga respective unipolar signal. The signals may be considered as unipolarsignals, or in combination with another electrode, as bipolar signals.Unipolar signals may be calculated with respect to the Wilson centralterminal (WCT), or with respect to another intracardiac electrode.

In a first part of the analysis of the signals, significant features,typically sections of the signals having a large numerical slope, areidentified. The analysis is performed for the unipolar signals (usingthe bipolar signals to improve the analysis). The analysis identifiesthe electrical activations, herein termed annotations, and assignsrespective quality factors to each of the annotations.

In a second part of the analysis, the atrial fibrillation signals arefurther investigated to identify blocked regions of the heart, i.e.,regions of the heart where cells have been temporarily saturated(refractory), so that they are unable to sustain, or are only partlyable to sustain, passage of an activation wave and subsequent detectionof annotations. The analysis can identify cells that are permanentlynon-conducting, such as cells of scar tissue.

The results of the two parts of the analysis may be incorporated into adynamic 3D map of the heart, showing progress of the activation wavethrough the heart, as well as blocked regions of the heart, i.e.,regions through which an activation wave does not pass.

There is provided according to embodiments of the invention a method,which is carried out by inserting a probe having electrodes into a heartof a living subject, recording a bipolar electrogram and a unipolarelectrogram from one of the electrodes at a location in the heart, anddefining a time interval including a window of interest wherein a rateof change in a potential of the bipolar electrogram exceeds apredetermined value. The method is further carried out by establishingan annotation in the unipolar electrogram, wherein the annotationdenotes a maximum rate of change in a potential of the unipolarelectrogram within the window of interest, assigning a quality value tothe annotation, and generating a 3-dimensional map of a portion of theheart that includes the annotation and the quality value thereof.

According to another aspect of the method, recording a bipolarelectrogram includes establishing a double bipolar electrodeconfiguration of electrodes. The double bipolar electrode configurationincludes a first differential signal from a first pair of unipolarelectrodes and a second differential signal from a second pair ofunipolar electrodes, wherein the bipolar electrogram is measured as atime-varying difference between the first differential signal and thesecond differential signal.

According to still another aspect of the method, establishing anannotation includes computing a wavelet transform of the unipolarelectrogram.

An additional aspect of the method includes producing a scalogram of thewavelet transform and determining the maximum rate of change in thescalogram.

Yet another aspect of the method includes determining from the qualityvalue that the annotation is a qualified annotation that meetspredetermined blocking criteria, and indicating on the map that thequalified annotation is at or near a blocked region of the heart.

According to still another aspect of the method, establishing anannotation includes removing ventricular far field components from theunipolar electrogram.

According to one aspect of the method, establishing an annotationincludes determining if a temporal cycle length of the unipolarelectrogram at the annotation lies within predefined statistical boundsfor temporal cycle lengths of other annotations.

An additional aspect of the method includes adjusting the quality valueof the annotation according to at least one of a quality value,inter-annotation distance and timing of another annotation.

According to another aspect of the method, the other annotation wasgenerated from another unipolar electrogram that was read from anotherof the electrodes.

A further aspect of the method includes filtering the unipolarelectrogram by an amount sufficient to reduce noise to a predeterminedlevel, wherein assigning a quality value includes determining theamount.

There is further provided according to embodiments of the invention anapparatus, including an intra-body probe having a plurality ofelectrodes. The probe is configured to contact tissue in a heart. Theapparatus includes a display, and a processor, which is configured toreceive an electrical signal from the electrodes and to perform thesteps of recording a bipolar electrogram and a unipolar electrogram fromone of the electrodes at a location in the heart, defining a timeinterval including a window of interest wherein a rate of change in apotential of the bipolar electrogram exceeds a predetermined value,establishing an annotation in the unipolar electrogram, wherein theannotation denotes a maximum rate of change in a potential of theunipolar electrogram within the window of interest, assigning a qualityvalue to the annotation, and generating on the display a 3-dimensionalmap of a portion of the heart wherein the map includes the annotationand the quality value thereof.

According to a further aspect of the apparatus, the probe has multiplerays, and each of the rays has at least one electrode.

According to one aspect of the apparatus, the probe is a basket catheterhaving multiple ribs, and each of the ribs has at least one electrode.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

For a better understanding of the present invention, reference is madeto the detailed description of the invention, by way of example, whichis to be read in conjunction with the following drawings, wherein likeelements are given like reference numerals, and wherein:

FIG. 1 is a pictorial illustration of a system for detecting areas ofabnormal electrical activity in a heart of a living subject inaccordance with an embodiment of the invention;

FIG. 2 is a group of bipolar electrograms, in accordance with anembodiment of the invention;

FIG. 3 is a diagram of a basket cardiac chamber mapping catheter for usein accordance with an embodiment of the invention;

FIG. 4 is a diagram of a spline catheter for use in accordance with anembodiment of the invention;

FIG. 5 is a flow chart of a method of annotating an electroanatomic mapof the heart in accordance with an embodiment of the invention;

FIG. 6 is a block diagram of unipolar local activation time detection inaccordance with an embodiment of the invention;

FIG. 7 is a detailed block diagram of an aspect of unipolar localactivation time detection shown in FIG. 6;

FIG. 8 is a detailed block diagram of the aspect of unipolar localactivation time detection shown in FIG. 7;

FIG. 9 is a chart illustrating signals that are processed according tothe diagram shown in FIG. 8;

FIG. 10 is a block diagram illustrating wavelet detection in accordancewith an embodiment of the invention;

FIG. 11 is a diagram illustrating signals produced by the arrangementshown in FIG. 10 in accordance with an embodiment of the invention;

FIG. 12 is a diagram illustrating wavelet transformation in differentarrhythmias in accordance with an embodiment of the invention;

FIG. 13 is a set of diagrams illustrating removal of an interferingsignal from a unipolar fibrillation signal in accordance with anembodiment of the invention;

FIG. 14 is a graphic diagram presenting an annotation of an electrogramin accordance with an embodiment of the invention;

FIG. 15 is a graphic diagram presenting annotations of electricalactivity in a case of atrial fibrillation in accordance with anembodiment of the invention; and

FIG. 16 is a graphic diagram presenting annotations of electricalactivity in accordance with an embodiment of the invention.

DETAILED DESCRIPTION OF THE INVENTION

In the following description, numerous specific details are set forth inorder to provide a thorough understanding of the various principles ofthe present invention. It will be apparent to one skilled in the art,however, that not all these details are necessarily needed forpracticing the present invention. In this instance, well-known circuits,control logic, and the details of computer program instructions forconventional algorithms and processes have not been shown in detail inorder not to obscure the general concepts unnecessarily.

DEFINITIONS

“Annotations” or “annotation points” refer to points or candidates on anelectrogram that are considered to denote events of interest. In thisdisclosure the events are typically onset (local activation time) of thepropagation of an electrical wave as sensed by the electrode.

“Activity” in an electrogram is used herein to denote a distinct regionof bursty or undulating changes in an electrogram signal. Such a regionmay be recognized as being outstanding between regions of baselinesignals. In this disclosure “activity” more often refers to amanifestation on an electrogram of one or more electrical propagationwaves through the heart.

Turning now to the drawings, reference is initially made to FIG. 1,which is a pictorial illustration of a system 10 for detecting areas ofelectrical activity in a heart 12 of a living subject 21 in accordancewith a disclosed embodiment of the invention. The system comprises aprobe, typically a catheter 14, which is percutaneously inserted by anoperator 16, who is typically a physician, through the patient'svascular system into a chamber or vascular structure of the heart. Theoperator 16 brings the catheter's distal tip 18 into contact with theheart wall at a target site that is to be evaluated. Unipolar andbipolar electrograms are recorded using mapping electrodes on the distalsegment of the catheter. Electrical activation maps based on theelectrograms are then prepared, according to the methods disclosed inthe above-noted U.S. Pat. Nos. 6,226,542, and 6,301,496, and in commonlyassigned U.S. Pat. No. 6,892,091, whose disclosure is hereinincorporated by reference.

The system 10 may comprise a general purpose or embedded computerprocessor, which is programmed with suitable software for carrying outthe functions described hereinbelow. Thus, although portions of thesystem 10 shown in other drawing figures herein are shown as comprisinga number of separate functional blocks, these blocks are not necessarilyseparate physical entities, but rather may represent, for example,different computing tasks or data objects stored in a memory that isaccessible to the processor. These tasks may be carried out in softwarerunning on a single processor, or on multiple processors. The softwaremay be provided to the processor or processors on tangiblenon-transitory media, such as CD-ROM or non-volatile memory.Alternatively or additionally, the system 10 may comprise a digitalsignal processor or hard-wired logic.

The catheter 14 typically comprises a handle 20, having suitablecontrols on the handle to enable the operator 16 to steer, position andorient the distal end of the catheter as desired to the ablation. To aidthe operator 16, the distal portion of the catheter 14 contains positionsensors (not shown) that provide signals to a positioning processor 22,located in a console 24. The catheter 14 may be adapted, mutatismutandis, from the ablation catheter described in commonly assigned U.S.Pat. No. 6,669,692, whose disclosure is herein incorporated byreference. The console 24 typically contains an ECG processor 26 and adisplay 30.

The positioning processor 22 measures location and orientationcoordinates of the catheter 14. In one embodiment, the system 10comprises a magnetic position tracking system that determines theposition and orientation of the catheter 14. The system 10 typicallycomprises a set of external radiators, such as field generating coils28, which are located in fixed, known positions external to the patient.The coils 28 generate electromagnetic fields in the vicinity of theheart 12. These fields are sensed by magnetic field sensors located inthe catheter 14.

Typically, the system 10 includes other elements, which are not shown inthe figures for the sake of simplicity. For example, the system 10 mayinclude an electrocardiogram (ECG) monitor, coupled to receive signalsfrom one or more body surface electrodes, so as to provide an ECGsynchronization signal to the console 24. The system 10 typically alsoincludes a reference position sensor, either on an externally-appliedreference patch attached to the exterior of the subject's body, or on aninternally-placed catheter, which is inserted into the heart 12maintained in a fixed position relative to the heart 12. Conventionalpumps and lines for circulating liquids through the catheter 14 forcooling an ablation site may be provided.

One system that embodies the above-described features of the system 10is the CARTO® 3 System, available from Biosense Webster, Inc., 3333Diamond Canyon Road, Diamond Bar, Calif. 91765. This system may bemodified by those skilled in the art to embody the principles of theinvention described herein. Multi-electrode basket and spline cathetersare known that are suitable for obtaining unipolar and bipolarelectrograms. An example of such a spline catheter is the Pentaray® NAVcatheter, available from Biosense Webster.

In order to better illustrate the difficulties that can be solved byapplication of the principles of the invention, reference is now made toFIG. 2, which is a group of bipolar electrograms, in accordance with anembodiment of the invention, in which a simulated bipolar electrode hasbeen positioned in eight directions. The bipolar electrograms have beencalculated from the difference of unipolar electrograms e.g., squares32, 34, shown in distinctive hatching patterns in an electroanatomic map36, in which one pole is fixedly positioned at the square 32 and theother pole is rotated in 8 steps (4 perpendicular and four obliquepositions) around the position of the fixed pole. On the map 36, anactivation wave propagates slightly obliquely from right to left. Themorphology observed from the eight bipolar complexes differs. This groupshows a complex activation, resulting from fusion of two waves, whichleads to large differences in morphology and amplitude of the bipolarcomplexes within windows of interest 38. FIG. 2 illustrates ambiguitiesin detection of activation. The local activation time at which theactivation wave passes a point is calculated by locating an event on anelectrogram meeting criteria to be described below and subtracting thetime of a fiducial reference from the time of the event. The time of thereference event may be defined using another intracardiac signal or bodysurface electrocardiogram.

The following two figures are schematic illustrations of distal ends ofcatheters used to acquire electropotentials from the heart, according toan embodiment of the present invention:

Reference is now made to FIG. 3, which is a diagram of a basket cardiacchamber mapping catheter 40 for use in accordance with an embodiment ofthe invention. The catheter 40 is similar in design to the basketcatheter described in U.S. Pat. No. 6,748,255, to Fuimaono, et al.,which is assigned to the assignees of the present invention and hereinincorporated by reference. The catheter 40 has multiple ribs, each ribhaving at multiple electrodes. In one embodiment the catheter 40 has 64unipolar electrodes, and can be configured with up to 7 bipolar pairsper spline. For example rib 42 has unipolar electrodes M1-M8, withbipolar configurations B1-B7. The inter-electrode distance is 4 mm.

Reference is now made to FIG. 4, which is a diagram of a spline catheter44 for use in accordance with an embodiment of the invention. An exampleof such a spline catheter is the Pentaray® NAV catheter, available fromBiosense Webster. The catheter 44 has multiple splines, each splinehaving several electrodes. In one embodiment the catheter 44 has 20unipolar electrodes, which can be configured as either two or threebipolar pairs per spline. For example, spline 46 has a first pair ofunipolar electrodes 48, 50 and a second pair of unipolar electrodes 52,54 (M1-M4). Respective differences between the unipolar electrode pairsare calculated in blocks 56, 58. The outputs of blocks 56, 58 (B1, B2)can be associated with one another to constitute a hybrid bipolarelectrode configuration, an arrangement referred to herein as a “doublebipolar configuration”. The double bipolar configuration is used toestablish a bipolar window of interest as described below. Possibleinter-electrode distances are 4-4-4 or 2-6-6 mm. Similar bipolarconfigurations can be established in the catheter 40 (FIG. 3).

Both of the catheters 38, 44 have multiple electrodes and are examplesof distal ends with multiple electrodes in their individual splines,spokes or branches, and the distal ends may be inserted into the heartof a patient. Embodiments of the present invention use catheters such asthe catheters 38, 44 to acquire time-varying electropotentialssimultaneously from different regions of the heart. In the case wherethe heart may be undergoing atrial fibrillation the acquiredelectropotentials are analyzed in order to characterize their transitwithin the heart.

Reference is now made to FIG. 5, which is a flow chart of a method ofannotating an electroanatomic map of the heart in accordance with anembodiment of the invention. The process steps are shown in a particularlinear sequence for clarity of presentation. However, it will be evidentthat many of them can be performed in parallel, asynchronously, or indifferent orders. Those skilled in the art will also appreciate that aprocess could alternatively be represented as a number of interrelatedstates or events, e.g., in a state diagram. Moreover, not allillustrated process steps may be required to implement the method.

The method comprises analyzing the electropotentials acquired bymultiple catheter electrodes while the subject is experiencing aconduction disturbance, e.g., atrial fibrillation. Initiallyelectropotential signals are acquired as bipolar potentials plotted overtime, typically by finding the differential signal between pairs ofadjacent electrodes. However, there is no necessity that the pairs ofelectrodes be adjacent, and in some embodiments bipolar signals fromnon-adjacent electrodes are used. For the bipolar signals information onthe 3-dimensional position of the electrodes may be used; alternativelyor additionally information on the electrode arrangement in the cathetermay be used.

In initial step 60 the bipolar signals are analyzed to determine initialtime periods, or windows, during which there is a relatively largechange in potential, i.e., a maximum value of

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Reference is now made to FIG. 6, which is a block diagram of a method ofunipolar local activation time (LAT) detection in accordance with anembodiment of the invention. A unipolar electrogram (EGM) input 62 isprocessed for removal of ventricular far field effects in a block 64.Far field reduction can be accomplished using the teachings of commonlyassigned patent application Ser. No. 14/166,982, entitled HybridBipolar/Unipolar Detection of Activation Wavefront, which is hereinincorporated by reference. Prefiltering occurs in block 66, and may beaccomplished using high and low pass filters, e.g. FIR and IIR filters.The output of block 66 is then processed in wavelet detection block 68,details of which are described below.

The output of block 66 forms an input 70 of double bipolar electrogramcalculation block 72. Another input 74 of block 72 carries theidentification of the electrodes being used for calculation of a bipolarelectrogram, as an output signal 76. Each member of a bipolar pair isconstructed as described with reference to the catheter 44 (FIG. 4). Forexample the inputs 70, 74 of block 72 could be unipolar electrodes 48,50 (FIG. 4) of the catheter 44. Block 56 of FIG. 4 corresponds to block72 of FIG. 6. Bipolar EGM onset and termination are established in block78. This may be accomplished using the teachings of commonly assignedU.S. Patent Application Publication No. 2013/0281870, which is hereinincorporated by reference. Windows of interest for the bipolarelectrogram are established using the outputs of block 68 and block 78in block 80.

Reference is now made to FIG. 7, which is a detailed block diagramillustrating the operation of block 72 (FIG. 6) in accordance with anembodiment of the invention. Two EGM inputs 82, 84 are pre-filtered andfar-field components removed in blocks 86, 88. The inputs 82, 84 aretypically generated from pairs of neighboring electrodes, each member ofa pair itself constituting a bipolar source, as shown in FIG. 3 and FIG.4. For example, the input 82 could be from unipolar electrode 50 (FIG.4). The outputs of blocks 86, 88 are subtracted in block 92, generatinga double bipolar output signal 94. The signal 94 is subjected to anotherpre-filtering step in block 96, denotched in block 98, and an outputsignal 100 submitted to block 102 wherein a bipolar window of interestis determined. An output signal 104 is produced by block 102.

Reference is now made to FIG. 8, which is a detailed block diagramillustrating a portion of the operation of block 102 (FIG. 7) inaccordance with an embodiment of the invention. Signals 106, 108, whichrepresent successive tentative window determinations (signal 104 (FIG.7)) are evaluated in window detection blocks 110, 112, which generateoutput signals 114, 116, respectively. A maximum between two minima isdetected. The signals 114, 116 are processed in block 118, where overlapof the detected windows is determined. In block 120 the windows found inblocks 110, 112 are fused, provided that there is an overlap thatexceeds 20%. A signal 122 indicative of a window of interest is outputby block 120.

Reference is now made to FIG. 9, which is a chart illustrating signalsthat are processed according to the arrangement of FIG. 8 in accordancewith an embodiment of the invention. Graphs 124, 126 represent outputsof blocks 110, 112 and show the morphology of the electrograms andrespective detected windows. For example, windows 128, 130 extensivelyoverlap and are therefore fused, as shown in graph 132. Graph 132indicates a superimposition of the electrograms of the graphs 124, 126and a fusion of the windows 128, 130 to form a larger window 134. Window134 begins at point 136, which is the minimum of the onset times of thewindows 128, 130 and ends at point 138, which is the maximum of thetermination times of the windows 128, 130.

Reference is now made to FIG. 10, which is a detailed block diagramillustrating the operation of wavelet detection block 68 (FIG. 6) inaccordance with an embodiment of the invention. Wavelet transformationprovides decomposition of a signal as a combination of a set of(orthonormal) basis functions derived from a mother wavelet by dilationand translation. If the wavelet is the derivative of a smoothingfunction, the wavelet coefficients represent the slope of the inputsignal. The wavelet parameters used in the arrangement of FIG. 10comprise: (1) a continuous wavelet transform (CWT); (2) the firstderivative of a Gaussian wavelet; and (3) decomposition over 15 linearscales in blocks 141, 143, followed by ratings and peak detection inblocks 145, 147.

Reference is now made to FIG. 11, which is a diagram illustratingsignals produced by the arrangement shown in FIG. 10 in accordance withan embodiment of the invention. Scalogram 140 is produced in wavelettransform block 142 from electrogram 144 by chaining maxima and minima;i.e., forming an ordered set of curves by an iterative filteringprocess. Intervals. For example intervals 146, 148 show readilyidentifiable maxima and minima in the scalogram 140, whereas these aremuch less distinct in the electrogram 144.

Reference is now made to FIG. 12, which is a diagram illustrating theoperation of wavelet transform block 68 (FIG. 6) in differentarrhythmias in accordance with an embodiment of the invention. Regionalelectroanatomic maps 150 indicate various types of atrial arrhythmicabnormalities that can be associated with atrial fibrillation. The maps150 are shown with corresponding electrograms 152 and scalograms 154.The scalograms 154 have distinct morphologies that relate to respectiveelectrograms 152. Generally the peaks in the electrograms 152 are moreclearly isolated in the scalograms 154, particularly when theactivations become less distinct, for example in the cases 156, 158 atthe right of the figure.

Reverting to FIG. 5, in a signal adjustment step 160 interfering signalsare removed from the unipolar fibrillation signals, in order to exposethe fibrillation signals. The interfering signals include ventricularfar field signals or components that are projected from the ventricle.In one way of removing these components, the signal emanating from theventricle is detected, and a mean QRS signal is subtracted, at the timeof generation of the ventricle signal, from the fibrillation signal.

Reference is now made to FIG. 13, which is a set of diagramsillustrating a process for removing an interfering signal from aunipolar fibrillation signal, in accordance with an embodiment of theinvention. As shown in a first part 162, a fibrillation signal initiallyincludes a ventricular far-field portion. A mean QRS signal isgenerated, typically from a set of QRS signals, as is shown in a secondpart 164, and, as shown in third and fourth parts 166, the fibrillationsignal is corrected by subtraction of the mean QRS signal.

Alternatively or additionally, template matching to a predefinedventricle signal, and/or a template based on an estimation from thefibrillation signal, at times where the signal is only ventricular, maybe used for prediction of the ventricular far field signal for theunipolar fibrillation signals. Typically, times for expected occurrenceof the ventricular signals may be determined from body ECG signals,ventricular intra-cardiac signals, or coronary sinus signals. Using thetemplate, the ventricular far field signals or components may beestimated and subtracted from the fibrillation signal.

Those having ordinary skill in the art will be able to adapt thedescription above, mutatis mutandis, for other methods of removal of theventricular far field signal. In addition, interfering signals otherthan the ventricular far field signals may be removed by similar methodsto those described above for the ventricular signals.

Other adjustments that may be performed in the signal adjustments stepinclude noise reduction (including 50/60 Hz signal induced noise),reduction of electro-magnetic interference (EMI), and correcting forbaseline drift, by any methods known in the art.

Returning to the flowchart of FIG. 5, in a further analysis step 168performed on the adjusted unipolar fibrillation signal, times, hereintermed annotations, a maximum

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value is detected are determined. The process of determining the maximum

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value is applied to the adjusted signal within the windows found in theinitial analysis initial step 60, and further includes a process ofnoise reduction. In one embodiment, the noise reduction applied to thecorrected fibrillation signal comprises forming a composition ofdifferent wavelet transforms with the corrected fibrillation signal. Thedifferent wavelet transforms effectively generate filters of differingbandwidths, and the composition of these filters with the correctedfibrillation signal reduces noise in the signal.

Additionally or alternatively, other methods for noise reduction, suchas by applying one or more different bandwidth filters to the signal,within the windows referred to above, may be applied to the correctedfibrillation signal.

In a quality estimation step 170, each maximum

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annotation may be assigned a parameter measuring the goodness of theannotation, depending on the amount and type of filtering required todetermine the annotation in step 168. For example, an annotationassigned with a high parameter value may be returned for both low andhigh levels of filtering, whereas an annotation assigned with a lowparameter value may be returned only for low or high filter levels, butnot for both.

The annotations are further characterized to estimate a final quality ofthe annotation. The characterization is according to the position of theelectrodes generating their signal, the location in the heart from wherethe signal was acquired, the timing of the annotation, the goodnessparameter of the annotation (determined in the previous step), and/orwhether the annotation is at or close to a time where signaladjustments, described above in the signal adjustment step, have beenmade. Each of these parameters may be assigned a numerical value. Forexample, from the position of a first electrode it may be consideredthat it is physiologically unlikely that the signal acquired by theelectrode will comprise an annotation, in which case the annotationfinal quality may be downgraded. For a second electrode it may beconsidered likely that the signal comprises an annotation, in which casethe annotation final quality may be upgraded.

In addition to the variables described above for estimating the qualityof a given annotation, the quality, inter-annotation distance and timingof neighboring spatial annotations may be checked, and the quality ofthe given annotation adjusted accordingly. For example, if a givenelectrode is surrounded by electrodes generating annotations with a highquality, then in some cases the quality of the given electrodeannotation may be increased (in other cases, described below withreference to step 28, there may be a blocking effect). Alternatively, ifa given electrode is surrounded by electrodes generating annotationswith a low quality, then the quality of the given electrode annotationmay be decreased. In addition, if a given electrode is surrounded byelectrodes generating quality annotations significantly outside aphysiological range, then the quality of the given electrode may befurther decreased.

As a further check to determine the quality of an annotation, theannotation is evaluated with respect to a statistic describing otherannotations. For example, a histogram of temporal cycle lengths of eachannotation may be generated. Only those annotations lying withinpredefined bounds of the histogram may be considered to be valid, andthose outside the bounds are assumed to be erroneous.

In a blocking identification step 172, the annotations meeting thecriteria assigned in step 170 are considered to identify regions of theheart where the activation of the heart muscle appears to have been“blocked.” Such a blockage occurs when activation waves collide or aredissociated, causing heart muscle cells at the position of collision tosaturate temporarily, so that they are unable to reactivate. These areknown as “refractory cells”. Blocked regions may be identified byconsidering the signal on a given electrode, as well as on thesurrounding electrodes. Typically, if the annotation signal on the givenelectrode is significantly smaller, has a different morphology, and/orhas a lower quality, than the annotation signals on surroundingelectrodes, then the given electrode may be considered to be located ator near a blocked region of the heart. A block may be temporary(functional block) or permanent (e.g., a scar).

In a presentation step 174, the results from the two previous steps,i.e., good quality annotations and regions identified as being blocked,are presented on a dynamic 3-dimensional map of the heart, or a chamberof the heart. Typically, the dynamic map illustrates the relative timingand the quality of the annotations in the heart, as well as an estimated“flow” of the annotations, i.e., time intervals between successiveannotations. The dynamic map also illustrates regions of the heart thatare assumed to be blocked. The dynamic map may also indicate regions ofthe heart, or of a chamber of the heart, from which no information wasobtained.

Reference is now made to FIG. 14, which is a graphic diagram presentingan annotation of an electrogram 176 in accordance with an embodiment ofthe invention. The lower portion of the figure details the processapplied to a representative complex 178. Hybrid bipolar windows 180, 182are obtained from two unipolar electrodes as described above. Tracings184, 186 represent the first derivatives of the signals from the twounipolar electrodes. A scalogram 188 was developed from wavelettransformations computed based on the electrogram 176. A series ofannotations 190 is shown on the scalogram 188.

Reference is now made to FIG. 15, which is a graphic diagram presentingannotations of electrical activity 192 in a case of atrial fibrillationin accordance with an embodiment of the invention. Tracings 194 aresuperimposed body surface electrode signals. Annotations are shown forseveral complexes in a scalogram 196 in the lower portion of the figure,and further indicated by the number of triangles in the lower portion ofthe figure. For example an annotation indicated by arrow 198 isassociated with only two triangles 200 and is of relatively low qualitycompared to an annotation indicated by arrow 202, which is associatedwith a larger number of triangles 204. The quality of the annotations isfurther graphically shown in middle portion 206. The technique hassuccessfully annotated a complex fractionated portion 208 of theactivity 192.

Reference is now made to FIG. 16, which is a graphic diagram presentingannotations of electrical activity in accordance with an embodiment ofthe invention. The presentation is similar to FIG. 15. The quality ofthe annotations is further indicated by dots 210. Dots 210 representchains starting from the finest scale and progressing to coarser scales.Inspection of the chains indicated by the dots 210 together with thechains indicated by the triangles that progress in the oppositedirection permits the operator to distinguish the various activationpatterns shown by scalograms 154 (FIG. 12).

It will be appreciated by persons skilled in the art that the presentinvention is not limited to what has been particularly shown anddescribed hereinabove. Rather, the scope of the present inventionincludes both combinations and sub-combinations of the various featuresdescribed hereinabove, as well as variations and modifications thereofthat are not in the prior art, which would occur to persons skilled inthe art upon reading the foregoing description.

1-19. (canceled)
 20. A method of determining quality of an annotationcomprising: identifying an annotation; and estimating a quality of theannotation based on one or more parameters selected from: an amount andtype of filtering required to determine the annotation; a position of aunipolar electrode generating its signal; a location in the heart fromwhere a signal was acquired; a timing of the annotation; or whether theannotation is at or close to a time where a signal adjustment has beenmade; assigning a value to the quality based on the on one or moreparameters; wherein the numerical value of the quality may be upgradedor downgraded based on the likelihood that the one or more parametersindicates an annotation.
 21. The method of claim 20, wherein for theparameter a position of a unipolar electrode generating its signal, thevalue is downgraded when, from a position of a first electrode, it isconsidered physiologically unlikely that a signal from the firstelectrode will comprise an annotation.
 22. The method of claim 20,further comprising: checking an inter-annotation distance, quality of aneighboring annotation and a timing of neighboring spatial annotations;adjusting the value of the quality based on the check.
 23. The method ofclaim 22, wherein if a first electrode is surrounded by a plurality ofsecond electrodes that are generating annotations with a high qualityvalue, then the quality value of an annotation from the first electrodeis increased.
 24. The method of claim 22, wherein if a first electrodeis surrounded by a plurality of second electrodes generating annotationswith a low quality, then the quality of the given electrode annotationmay be decreased.
 25. The method of claim 22, wherein if a firstelectrode is surrounded by plurality of second electrodes generatingannotations significantly outside a predetermined physiological range,then the quality of the given electrode is decreased.
 26. The method ofclaim 20, further comprising evaluating the quality of an annotationwith respect to a statistic describing other annotations.
 27. The methodof claim 26, wherein the statistic comprises a histogram of temporalcycle lengths of each annotation; and wherein annotations lying withinpredefined bounds of the histogram are considered to be valid, and thoseoutside the bounds are considered to be erroneous.
 28. A method ofremoving an interfering signal from a unipolar fibrillation signal, themethod comprising: receiving a unipolar electrogram; generating a QRStemplate; and subtracting the QRS template from the unipolarelectrogram.
 29. The method of claim 28, wherein the generating stepfurther comprises: identifying plurality of occurrences of QRS episodesin the unipolar electrogram; identifying a mean of the plurality of QRSepisodes; and generating the QRS template from the mean of the pluralityof QRS episodes.
 30. The method of claim 28, wherein the generating stepfurther comprises generating a QRS template from a predefined ventriclesignal.
 31. The method of claim 28, wherein the generating step furthercomprises estimating a ventricular far field signal from a fibrillationsignal at times where the signal is only ventricular.
 32. The method ofclaim 28, further comprising: identifying a plurality of occurrences ofQRS episodes in the unipolar electrogram from one or more of a body ECGsignal, a ventricular intra-cardiac signal, or a coronary sinus signal.33. The method of claim 28, wherein the subtracting step comprises:identifying times for each occurrence of a plurality of QRS episodes inthe unipolar electrogram; subtracting the QRS signal from the unipolarelectrogram at the time identified for each occurrence of a plurality ofQRS episodes.